Carcinomas comprise about 90% of all human tumors and arise through the genetic alteration of epithelial[unreadable] cells. Many human carcinomas, including those of the breast, consist of neoplastic epithelial cells[unreadable] intermingled with a complex mixture of cells, including fibroblasts, myofibroblasts, endothelial cells and[unreadable] immune cells, which collectively form the tumor stroma. The supporting stroma of a carcinoma is distinct[unreadable] from that found in the adjacent normal tissue, and as the carcinoma expands, these stromal cells are[unreadable] recruited and induced to proliferate. The presence of stromal cell types within carcinomas is a powerful[unreadable] determinant of the biology of a tumor through its ability to have profound influences on the growth, survival,[unreadable] invasiveness, and metastatic powers of the neoplastic epithelial cells. The presence of these cells has been[unreadable] demonstrated by our laboratory and others to have an essential role in supporting tumor progression;[unreadable] however, the mechanisms of stromal recruitment and how these cells contribute to tumor growth are not well[unreadable] understood.[unreadable] The proposed studies are directed at elucidating the recruitment of stromal cells and the mechanisms by[unreadable] which they influence tumor progression by accomplishing the following:[unreadable] A1. Determining the origins of the tumor-associated stromal cells;[unreadable] A2. Determining the nature of the signals used to recruit stromal precursor cells;[unreadable] A3. Characterizing the heterotypic signals released by recruited stromal cells that[unreadable] influence invasion and metastasis by carcinoma cells;[unreadable] A4. Determining the mechanisms by which mesenchymal stem cells can enhance[unreadable] metastatic ability.